Relevance of breast cancer cell lines as models for breast tumours : a review incorporating microarray data.

scimedweb scimedweb at mail.com
Wed Feb 11 04:16:12 EST 2004

"Relevance of breast cancer cell lines as models for breast tumours :
an update"
by Marc Lacroix and Guy Leclercq


The number of available breast cancer cell (BCC) lines is small, and
only a very few of them have been extensively studied. Whether they
are representative of the tumours from which they originated remains a
matter of debate. Whether their diversity mirrors the well-known
inter-tumoral heterogeneity is another essential question. While
numerous similarities have long been found between cell lines and
tumours, recent technical advances, including the use of micro-arrays
and comparative genetic analysis, have brought new data to the
discussion. This paper presents most of the BCC lines that have been
described in some detail to date. It evaluates the accuracy of the few
of them widely used (MCF-7, T-47D, BT-474, SK-BR-3, MDA-MB-231,
Hs578T) as tumour models. It is concluded that BCC lines are likely to
reflect, to a large extent, the features of cancer cells in vivo. The
importance of oestrogen receptor-alpha (gene ESR1) and Her-2/neu
(ERBB2) as classifiers for cell lines and tumours is underlined. The
recourse to a larger set of cell lines is suggested since the exact
origin of some of the widely used lines remains ambiguous.
Investigations on additional lines is expected to improve our
knowledge of BCC and of the dialogue that these maintain with their
surrounding normal cells in vivo.

1. Presentation of BCC lines - The question of representativeness 
1.1) Multiplicity and variability of BCC lines 
A) Distinctive features of BCC lines
B) BCC lines series 
"HCC (Hamon Cancer Centre) series"
"SUM series"
"HMT series"
C) BCC lines variants
D) BCC lines from breast cancer patients with germ line mutations
E) The specificity of inflammatory breast cancer
1.2) The problem of BCC lines representativeness
2. Phenotype and invasiveness-based studies of BCC lines and tumours 
2.1) Phenotype and invasiveness-based BCC line classification 
A) Steroid receptor status and the bias in BCC line isolation
B) Distinct phenotypes - The "epithelial-mesenchymal transition" (EMT)
C) Extended marker analysis
2.2) Analysis of breast tumours - Markers and grade - Comparison with
cell lines
A) Molecular markers
B) Grade
2.3) Macroscopic homogeneity of breast tumours - Stable "portrait"
during progression
A) Progression to invasiveness and markers/grade
B) Recurrence, metastasis
2.4) Concluding remarks on phenotype studies
3. Genetic studies on BCC lines and tumours 
3.1) Karyotype and cytogenetic studies on BCC lines and tumours
3.2) Extension of genetic analyses: micro-array studies 
A) BCC lines
B) Tumours
C) Comparison of genetic profiles of BCC lines and tumours
3.3) Epigenetic alterations - Hypermethylation
4. Dialogue between tumour cells and their cellular environment
5. Tumourigenicity of BCC lines in animal models
To which extent are individual tumours genetically and phenotypically
Do BCC cultured in vitro maintain the characteristics that they had in
Do the panel of widely used BCC lines accurately reflect the variety
of tumour phenotypes?

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